The rapid induction of muscle-specific gene products accompanying the fusion of cultured myoblasts to myotubes that is seen after removal of the mitogenic stimulus of serum and the addition of insulin has been intensively studied. We investigated the effect of removal and re-addition of insulin on the stability of induced mRNAs during and after differentiation of rat L6A1 myoblast cells in culture. Addition of insulin caused an 80 fold increase in creatine phosphokinase (CK) activity, a similar increase in CK mRNA, and a parallel increase in myosin heavy chain (MHC) mRNA. Removal of insulin caused CK mRNA, but not MHC mRNA, to be rapidly degraded, the effect being reversed when the hormone was added back. Cycloheximide and actinomycin D mimic the action of the inducer also in a reversible manner, indicating that a short-lived protein(s) encoded by a shot- lived mRNA(s) selectively regulates the stability of inducible mRNA. Such factor(s) may be an important requirement for normal developmental processes.